Glucosamine is a popular over-the-counter nutritional supplement that many people use for the treatment of osteoarthritis. Intravenous administration of glucosamine to animals or humans causes significant metabolic insulin resistance and vascular endothelial dysfunction. Moreover, experiments with various cell lines have implicated elevated glucosamine levels in the development of insulin resistance. However, there are no published studies examining the potential effects of oral glucosamine administration to modulate insulin sensitivity or capillary recruitment in humans. This is a significant concern because insulin resistance and vascular dysfunction contribute importantly to major public health problems including diabetes, obesity, hypertension, and cardiovascular diseases. Normal healthy volunteers and obese insulin resistant subjects will be enrolled in a randomized double-blind, placebo-controlled, crossover study to evaluate the effects of oral glucosamine to modulate insulin sensitivity and insulin-stimulated capillary recruitment. The reference standard hyperinsulinemic isoglycemic glucose clamp technique will be used to assess insulin sensitivity before treatment, after placebo or oral glucosamine (500 mg p.o. TID for 6 weeks), and after completion of the crossover. In addition, insulin-stimulated capillary recruitment will be measured at the same time as the glucose clamp studies by using an ultrasound technique with microbubble contrast to assess blood flow in the brachial artery and capillary recruitment in forearm skeletal muscle in response to hyperinsulinemia. Finally, plasma glucosamine levels will be measured just prior to each glucose clamp study using an HPLC method. The results of this study will determine if oral glucosamine administration causes significant insulin resistance and impairment in insulin-stimulated capillary recruitment in healthy volunteers or worsens insulin resistance and capillary recruitment in obese subjects. In addition, our study will provide important information about how plasma glucosamine levels change with commonly used oral doses of glucosamine.